Efficacy and Safety of Losmapimod in Treating Subjects With Facioscapulohumeral Muscular Dystrophy (FSHD) With Open-Label Extension (OLE)

NCT04264442 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: FIS-002-2019 OLE
• Study Type: interventional
• Target: 76
• Locations: 4 countries
• Sites: 17

Brief Summary

This study is an open-label extension to evaluate the safety and tolerability of long-term dosing of Losmapimod in patients with FSHD1 who participated in the ReDux4 study.

Conditions

Facioscapulohumeral Muscular Dystrophy (FSHD)

Keywords

FSHD, FSHD1; Muscular Dystrophy; Muscular Dystrophies; Facioscapulohumeral Muscular Disorders; Musculoskeletal Diseases; Neuromuscular Diseases

Outcome Measures

Primary Outcomes (8)

• Number of Participants Reporting Serious Treatment Emergent Adverse Events (Serious TEAEs) and TEAEs

  A TEAE is an adverse event that begins on or after the first dose of study drug and on or before the stop of study drug plus 7 days or begins before the first dose of study drug and worsens on or after the first dose of study drug and on or before the stop of study drug plus 7 days. An adverse event with completely missing onset and end dates was considered as TEAE. An adverse event with missing onset date but the end date is on or after the first dose of study drug and before the stop of study drug plus 7 days was considered a TEAE.

  Up to 57 months

• Number of Participants With Clinically Significant Changes in Chemistry Parameters

  Blood samples were collected for the analysis of chemistry parameters: Glucose, sodium, potassium, calcium, inorganic phosphate, total protein, albumin, blood urea nitrogen, creatinine, total bilirubin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transferase and creatine phosphokinase.

  Up to 57 months

• Number of Participants With Clinically Significant Changes in Hematology Parameters

  Blood samples were collected for the analysis of hematology parameters: hemoglobin (including mean corpuscular volume), mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, hematocrit, red blood cell count, total white blood cell count, platelet count. Differential blood counts, including basophils, eosinophils, neutrophils, lymphocytes, and monocytes

  Up to 57 months

• Number of Participants With Clinically Significant Changes in Serum Coagulation Parameters

  Blood samples were collected for the analysis of Serum coagulation parameters: International normalized ratio, prothrombin time, partial thromboplastin time.

  Up to 57 months

• Number of Participants With Clinically Significant Changes in Urinalysis

  Urine samples were collected for the analysis of urinalysis parameters: Leucocytes, blood, nitrite, protein, urobilinogen, bilirubin, pH, specific gravity, ketones, glucose.

  Up to 57 months

• Number of Participants With Clinically Significant Changes in Vital Parameters

  Vital parameters including pulse rate, respiration rate, blood pressure, and temperature were measured in seated or recumbent for at least 5 minutes. Data for number of participants with abnormal clinically significant changes for vital signs have been presented.

  Up to 57 months

• Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Parameters

  Twelve-lead ECGs was performed after participants has been recumbent for at least 5 minutes.

  Up to 57 months

• Number of Participants With Clinically Significant Changes in Physical Examinations

  Physical examinations included an evaluation of body systems, including but not limited to the following: skin; head, eyes, ears, nose, and throat; respiratory system; cardiovascular system; abdomen (liver, spleen); lymph nodes; neurological system; and musculoskeletal system.

  Up to 57 months

Study Arms (1)

Losmapimod

EXPERIMENTAL

FSHD1 patients with genetic confirmation will receive Losmapimod 15 mg by mouth twice daily for a total of 30 mg daily until 90 days after commercial drug is available post regulatory approval or until the study is discontinued by the Sponsor.

Drug: Losmapimod

Interventions

Losmapimod DRUG

Patients will receive Losmapimod 15 mg by mouth twice daily for a total of 30 mg daily until 90 days after commercial drug is available post regulatory approval or until the study is discontinued by the Sponsor. The study drug should be taken with food and the date and time of each dose taken should be recorded in the subject diary.

Losmapimod

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The patient must have consented to participate and must have provided signed, dated and witnessed an IRB-approved informed consent form that conforms to federal and institutional guidelines.
• Male or female subjects
• Patients must be between 18 and 65 years of age, inclusive
• Must be willing and able to comply with scheduled visits, treatment plan, study restrictions, laboratory tests, contraceptive guidelines and other study procedures.
• Will practice an approved method of birth control

You may not qualify if:

• Has a history of any illness or any clinical condition that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering study drug to the subject. This may include, but is not limited to, a history of relevant drug or food allergies; history of cardiovascular or central nervous system disease; neuromuscular diseases except FSHD (eg, myopathy, neuropathy, neuromuscular junction disorders); or clinically significant history of mental disease.
• For subjects who are on drug(s) or supplements that may affect muscle function, as determined by the treating physician, or that are included in the list of drugs presented in the protocol, subjects must be on a stable dose of that drug(s) or supplement for at least 3 months prior to the first dose of study drug and remain on that stable dose for the duration of the study. Changes to the dose or treatment discontinuation during the study can only be done for strict medical reasons by the treating physician with clear documentation and notification to the sponsor.

Sponsors & Collaborators

• Fulcrum Therapeutics: lead

Study Sites (17)

University of California Irvine

Irvine, California, 92868, United States

Location

University of California Los Angeles (UCLA)

Los Angeles, California, 90095, United States

Location

University of Florida

Gainesville, Florida, 32610, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Kennedy Krieger Institute

Baltimore, Maryland, 21205, United States

Location

University of Massachusetts Memorial Medical Center

Worcester, Massachusetts, 01655, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

Ohio State University

Columbus, Ohio, 43221, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

University of Washinton Medical Center

Seattle, Washington, 98195, United States

Location

Ottawa Hospital Research Institute

Ottawa, Ontario, K1Y 4E9, Canada

Location

Montreal Neurological Institute and Hospital

Montreal, Quebec, H3A 2B4, Canada

Location

CHU de NICE- CHU pasteur2

Nice, 06001, France

Location

Hospital de la Sta Creu i St Pau

Barcelona, 08041, Spain

Location

Hospital UiP La Fe

Valencia, 46026, Spain

Location

Related Publications (7)

• Barbour AM, Sarov-Blat L, Cai G, Fossler MJ, Sprecher DL, Graggaber J, McGeoch AT, Maison J, Cheriyan J. Safety, tolerability, pharmacokinetics and pharmacodynamics of losmapimod following a single intravenous or oral dose in healthy volunteers. Br J Clin Pharmacol. 2013 Jul;76(1):99-106. doi: 10.1111/bcp.12063.

  PMID: 23215699 BACKGROUND

• Cheriyan J, Webb AJ, Sarov-Blat L, Elkhawad M, Wallace SM, Maki-Petaja KM, Collier DJ, Morgan J, Fang Z, Willette RN, Lepore JJ, Cockcroft JR, Sprecher DL, Wilkinson IB. Inhibition of p38 mitogen-activated protein kinase improves nitric oxide-mediated vasodilatation and reduces inflammation in hypercholesterolemia. Circulation. 2011 Feb 8;123(5):515-23. doi: 10.1161/CIRCULATIONAHA.110.971986. Epub 2011 Jan 24.

  PMID: 21262998 BACKGROUND

• de Greef JC, Lemmers RJ, van Engelen BG, Sacconi S, Venance SL, Frants RR, Tawil R, van der Maarel SM. Common epigenetic changes of D4Z4 in contraction-dependent and contraction-independent FSHD. Hum Mutat. 2009 Oct;30(10):1449-59. doi: 10.1002/humu.21091.

  PMID: 19728363 BACKGROUND

• Han JJ, Kurillo G, Abresch RT, de Bie E, Nicorici A, Bajcsy R. Reachable workspace in facioscapulohumeral muscular dystrophy (FSHD) by Kinect. Muscle Nerve. 2015 Feb;51(2):168-75. doi: 10.1002/mus.24287. Epub 2014 Nov 19.

  PMID: 24828906 BACKGROUND

• Jagannathan S, Shadle SC, Resnick R, Snider L, Tawil RN, van der Maarel SM, Bradley RK, Tapscott SJ. Model systems of DUX4 expression recapitulate the transcriptional profile of FSHD cells. Hum Mol Genet. 2016 Oct 15;25(20):4419-4431. doi: 10.1093/hmg/ddw271.

  PMID: 28171552 BACKGROUND

• Statland JM, Tawil R. Risk of functional impairment in Facioscapulohumeral muscular dystrophy. Muscle Nerve. 2014 Apr;49(4):520-7. doi: 10.1002/mus.23949. Epub 2014 Feb 10.

  PMID: 23873337 BACKGROUND

• Wang LH, Friedman SD, Shaw D, Snider L, Wong CJ, Budech CB, Poliachik SL, Gove NE, Lewis LM, Campbell AE, Lemmers RJFL, Maarel SM, Tapscott SJ, Tawil RN. MRI-informed muscle biopsies correlate MRI with pathology and DUX4 target gene expression in FSHD. Hum Mol Genet. 2019 Feb 1;28(3):476-486. doi: 10.1093/hmg/ddy364.

  PMID: 30312408 BACKGROUND

MeSH Terms

Conditions

Muscular Dystrophy, Facioscapulohumeral; Muscular Dystrophies; Musculoskeletal Diseases; Neuromuscular Diseases

Interventions

6-(5-((cyclopropylamino)carbonyl)-3-fluoro-2-methylphenyl)-N-(2,2-dimethylprpyl)-3-pyridinecarboxamide

Condition Hierarchy (Ancestors)

Muscular Disorders, Atrophic; Muscular Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Results Point of Contact

• Title: Call Center
• Organization: Fulcrum Therapeutics

clinicaltrials@fulcrumtx.com

617-651-8853

Study Officials

• Marie-Helene Jouvin, MD

  Fulcrum Therapeutics

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This study is part two of NCT04003974 which was a randomized, double-blind placebo-controlled treatment period for 48 weeks. This study is an open-label extension with losmapimod in patients with FSHD1.

Study Record Dates

• First Submitted: January 30, 2020
• First Posted: February 11, 2020
• Study Start: February 13, 2020
• Primary Completion: November 7, 2024
• Study Completion: November 7, 2024
• Last Updated: September 30, 2025
• Results First Posted: September 30, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

CA (2); US (12); FR (1); ES (2)